The Chiefs said his return to the game was questionable.
Charles was injured when he was tackled by Indianapolis' Greg Toler on a seven-yard run. Charles was helped to the sideline, where he was examined by team doctors. He was later escorted to the locker room.
The sixth-year running back led the AFC in rushing with 1,287 yards, led the Chiefs (11-5) with 70 receptions for 693 yards and seven TDs. His 19 total touchdowns led the NFL.
Charles was replaced by rookie Knile Davis.
Information from The Associated Press was used in this report.